title: Active immunisation of human interferon α transgenic mice with a human interferon α Kinoid induces antibodies that neutralise interferon α in sera from patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  Interferon α (IFNα) plays a central role in the pathogenesis of systemic lupus erythematosus (SLE) and is considered a target for its treatment. In the current study, the ability of active immunisation with a human (hu) IFNα2b Kinoid (IFN-K) to break B cell tolerance to IFNα and to induce huIFNα-neutralising antibodies in mice immunotolerant to huIFNα2b was assessed.
  
  
  METHODS
  IFN-K was manufactured by crosslinking huIFNα2b to keyhole limpet haemocyanin (KLH). Transgenic mice expressing huIFNα2b received by intramuscular injection either saline or polymerised huIFNα2b as controls, or IFN-K, emulsified in ISA51vg adjuvant.
  
  
  RESULTS
  All of the huIFNα2b-expressing mice immunised with IFN-K generated neutralising antibodies against huIFNα2b. In addition, these antibodies neutralised all 13 subtypes of huIFNα. They also neutralised IFNα activity in sera collected from 10 different patients with active SLE. However, the antibodies did not bind to huIFNγ or huIFNβ. Finally, cellular activation assays showed that immunisation with IFN-K did not induce memory T cells reactive to native huIFNα2b, whereas it did induce memory cells reactive to KLH.
  
  
  CONCLUSIONS
  These results show that active immunisation with IFN-K induces polyclonal antibodies that neutralise all subtypes of huIFNα as well as IFNα in sera from patients with SLE by breaking humoral but not cellular tolerance to IFNα. This suggests that immunisation with IFN-K is a promising new therapeutic strategy for the treatment of SLE.
authors.affiliation: Service de Médecine Interne, Centre de Référence National pour Lupus et Syndrome des Antiphospholipides, CHU Pitié-Salpêtrière, APHP, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Estelle
authors.initials: E
authors.lastname: Adam
authors.forename: Fabien
authors.initials: F
authors.lastname: Colaone
authors.forename: Marco F M
authors.initials: MF
authors.lastname: Hoekman
authors.forename: Olivier
authors.initials: O
authors.lastname: Dhellin
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapelière
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.forename: Géraldine
authors.initials: G
authors.lastname: Grouard-Vogel
mesh_terms: D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin